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Development of a reliable test system for purinergic P2X3 receptors
Tomanová, Šárka ; Doležal, Martin (advisor) ; Pourová, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Šárka Tomanová Supervisors: Prof. PharmDr. Martin Doležal, Ph.D., Prof. Dr. Christa Elisabeth Müller Title of diploma thesis: Development of a reliable test system for purinergic P2X3 receptors Purinergic P2X3 receptor is a ligand-gated ionotropic channel that occurs in all mammalian tissues. The highest occurrence has been observed in central and peripheral nervous system and smooth muscles, where P2X3 receptors participate in pathological disorders such as visceral and neurophatic pain, inflammatory reactions and psychiatric disorders. Compounds capable of blocking P2X3 receptor activity could be therefore used as potential drugs for treatment of these states. P2X3 receptor belongs to fast- desensitizing ionotropic channels, which makes the measurement of its activity very difficult. It was described that one point S15V mutation, in which the amino acid serine in a position 15 is replaced by amino acid valine, slows down the desensitization rate and the signal becomes easily measurable. This simple mutation may be used as an effective tool for characterization of insufficiently explored P2X3 receptor. The P2X3 S15V receptor DNA was inserted into retrovirus and,...
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